huMNC2-CAR-1XX

huMNC2-CAR-1XX (also known as huMNC2-CAR22 or MUC1*-CAR-1XX) is an autologous chimeric antigen receptor (CAR) T-cell therapy being developed by Minerva Biotechnologies for the treatment of solid tumors, specifically metastatic breast cancer. The therapy consists of a patient's own T cells engineered to express a CAR targeting MUC1* (muk 1 star), a cleaved growth factor receptor form of mucin 1 (MUC1) that is highly expressed on cancerous tissues but absent on normal epithelial cells. The CAR construct utilizes a humanized MNC2 single-chain variable fragment (huMNC2-scFv) as the targeting head, a CD28 co-stimulatory domain, and a CD3-ζ signaling domain containing the '1XX' mutation (four tyrosine-to-phenylalanine substitutions in ITAMs 2 and 3). This mutation slows CAR T-cell signaling, which prevents T-cell exhaustion, increases in vivo persistence, and enables the cells to effectively eliminate low-antigen-expressing cancer cells. The drug is currently being evaluated in Phase 1/2 clinical trials.

Other names

MUC1*-targeted CAR T bearing 1XX mutationsautologous huMNC2-CAR22 T cellshuMNC2-CD28-CD3ζ-1XX